Insulin resistant subjects lack islet adaptation to short-term dexamethasone-induced reduction in insulin sensitivity

Diabetologia. 1999 Aug;42(8):936-43. doi: 10.1007/s001250051251.

Abstract

Aims/hypothesis: To establish whether islet compensation to deterioration of insulin action depends on inherent insulin sensitivity.

Methods: We examined insulin and glucagon secretion after i.v. arginine (5 g) at fasting, 14 and greater than 25 mmol/l glucose concentrations before and after lowering of insulin sensitivity by oral dexamethasone (3 mg twice daily for 2 1/2 days) in 10 women with normal glucose tolerance, aged 58 or 59 years. Five women had high insulin sensitivity as shown by euglycaemic, hyperinsulinaemic clamp (99 +/- 12 nmol glucose.kg body weight-1.min-1/pmol insulin.l-1; means +/- SD) whereas five women had low insulin sensitivity (34 +/- 15 nmol glucose.kg body weight-1.min-1/pmol insulin.l-1).

Results: Dexamethasone reduced insulin sensitivity in both groups. Fasting insulin concentration increased by dexamethasone in high insulin sensitivity (72 +/- 10 vs 49 +/- 9 pmol/l, p = 0.043) but not in low insulin sensitivity (148 +/- 63 vs 145 +/- 78 pmol/l) whereas the fasting glucose concentration increased in low insulin sensitivity (6.5 +/- 0.8 vs 5.8 +/- 0.6 mmol/l, p = 0.043) but not in high insulin sensitivity (5.3 +/- 0.8 vs 5.3 +/- 0.6 mmol/l). Fasting glucagon concentration was not changed. Plasma insulin concentrations after raising glucose to 14 and more than 25 mmol/l and the insulin response to arginine at more than 25 mmol/l glucose were increased by dexamethasone in high insulin sensitivity (p < 0.05) but not changed by dexamethasone in low insulin sensitivity. Furthermore, in high but not in low insulin sensitivity, dexamethasone reduced the glucagon response to arginine (p = 0.043).

Conclusion/interpretation: The results show that adaptation in islets function to dexamethasone-induced short-term reduction in insulin sensitivity is lacking in subjects with low inherent insulin sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine
  • Blood Glucose / metabolism
  • Dexamethasone* / pharmacology
  • Fasting
  • Female
  • Glucagon / blood
  • Glucagon / metabolism*
  • Glucocorticoids
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Glycated Hemoglobin / analysis
  • Humans
  • Infusions, Intravenous
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin / pharmacology*
  • Insulin Resistance / physiology*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Middle Aged
  • Postmenopause

Substances

  • Blood Glucose
  • Glucocorticoids
  • Glycated Hemoglobin A
  • Insulin
  • Dexamethasone
  • Glucagon
  • Arginine